An adenine compound represented by the following formula (1):
wherein m, n, R1, R2, R3 and R4 are the same as defined below, or a pharmaceutically acceptable salt thereof is known to be useful as a medicament (See patent documents 1 and 2).
It is described in patent document 1 that methyl (3-{[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purine-9-yl)propyl](2-morpholin-4-ylethyl)amino]methyl}phenyl)acetate is prepared by reacting 9-(3-aminopropyl)-2-butoxy-8-methoxy-9H-purine-6-amine with methyl 3-formylphenyl acetate, and then alkylating the reacted compound with 2-morpholinoethyl chloride, followed by treating with an acid, and so on.
Furthermore, it is described in patent document 1 that methyl (3-{[[4-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purine-9-yl)butyl](3-morpholin-4-ylpropyl)amino]methyl}phenyl)acetate is prepared by reacting 9-(4-bromobutyl)-2-butoxy-8-methoxy-9H-purine-6-amine with N-(3-aminopropyl)morpholine, and treating the reacted product with an acid, followed by alkylation with methyl 3-bromomethylphenylacetate, and so on.
Furthermore, it is described in patent document 2 that methyl (3-{[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purine-9-yl)propyl](3-dimethyaminopropyl)amino]methyl}phenyl)acetate is prepared by treating 9-(3-bromopropyl)-2-butoxy-8-methoxy-9H-purine-6-amine with an acid, and then reacting it with 3-hydroxypropylamine, methyl 3-bromomethylphenylacetate, mesyl chloride and dimethylamine, successively, and so on.
However, according to these methods, in case of an alkylation step by substitution reaction with a primary amine and an alkyl halide, or by reductive amination of an aldehyde, there is a problem that not only an objective monoalkylated compound but also dialkylated compound, a by-product is produced. Furthermore, in case of the above formula (1) wherein m is 3 or 4, there is a possibility to produce a tricyclic compound bridged between positions 9 and 8 of the purine nucleus, or between positions 9 and 3 of the purine nucleus or a by-product derived from β-elimination.
Furthermore, in case of a compound having an leaving group such as 9-(3-bromopropyl)-2-butoxy-8-methoxy-9H-purine-6-amine, etc., there is a problem (possibility) to produce a by-product represented by the following formula (11) which are formed by condensation of two molecules.
wherein m and R1 is the same as define below.
As mentioned above, a method for preparing a compound represented by the formula (1) which is produced in a high yield with controlling a production of by-products has been desired.    Patent document 1: WO 2005/092893 gazette    Patent document 2: WO 2007/031726 gazette